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Temperature-Tunable Iron Oxide Nanoparticles for Remote-Controlled Drug Release

  • Research Article
  • Theme: Translational Application of Nano Delivery Systems: Emerging Cancer Therapy
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Abstract

Herein, we report the successful development of a novel nanosystem capable of an efficient delivery and temperature-triggered drug release specifically aimed at cancer. The water-soluble 130.1 ± 0.2 nm iron oxide nanoparticles (IONPs) were obtained via synthesis of a monodispersed iron oxide core stabilized with tetramethylammonium hydroxide pentahydrate (TMAOH), followed by coating with the thermoresponsive copolymer poly-(NIPAM-stat-AAm)-block-PEI (PNAP). The PNAP layer on the surface of the IONP undergoes reversible temperature-dependent structural changes from a swollen to a collapsed state resulting in the controlled release of anticancer drugs loaded in the delivery vehicle. We demonstrated that the phase transition temperature of the prepared copolymer can be precisely tuned to the desired value in the range of 36°C–44°C by changing the monomers ratio during the preparation of the nanoparticles. Evidence of modification of the IONPs with the thermoresponsive copolymer is proven by ATR-FTIR and a quantitative analysis of the polymeric and iron oxide content obtained by thermogravimetric analysis. When loaded with doxorubicin (DOX), the IONPs-PNAP revealed a triggered drug release at a temperature that is a few degrees higher than the phase transition temperature of a copolymer. Furthermore, an in vitro study demonstrated an efficient internalization of the nanoparticles into the cancer cells and showed that the drug-free IONPs-PNAP were nontoxic toward the cells. In contrast, sufficient therapeutic effect was observed for the DOX-loaded nanosystem as a function of temperature. Thus, the developed temperature-tunable IONPs-based delivery system showed high potential for remotely triggered drug delivery and the eradication of cancer cells.

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Acknowledgments

This work was supported in part by the funding provided by the Medical Research Foundation of Oregon, PhRMA Foundation and the College of Pharmacy, Oregon State University. We thank Teresa Sawyer (Electron Microscopy Facility, OSU) for TEM analysis and Dr. Christine Pastorek (Department of Chemistry, OSU) for access to the FTIR-ATR and TGA instruments.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 1601 SW Jefferson Street, Corvallis, Oregon, 97331, USA

    Raj K. Dani, Canan Schumann, Olena Taratula & Oleh Taratula

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  1. Raj K. Dani
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  2. Canan Schumann
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  3. Olena Taratula
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  4. Oleh Taratula
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Correspondence to Olena Taratula or Oleh Taratula.

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Guest Editors: Mahavir B. Chougule and Chalet Tan

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Dani, R.K., Schumann, C., Taratula, O. et al. Temperature-Tunable Iron Oxide Nanoparticles for Remote-Controlled Drug Release. AAPS PharmSciTech 15, 963–972 (2014). https://doi.org/10.1208/s12249-014-0131-x

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  • DOI: https://doi.org/10.1208/s12249-014-0131-x

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